PB2243: TREATMENT OF TWO JORDANIAN SIBLINGS WITH CONGENITAL DYSERYTHROPOEITIC ANEMIA - TYPE 1BUSING INTERFERON-ALPHA-2A
Authors: E. Khattab, M. abu shanap, R. rihani, H. hashem, I. Sultan
Journal: HemaSphere (2022)

Background: Congenital dyserythropoietic anemias (CDAs) are a group of rare hereditary congenital anemias characterized by marked ineffective erythropoiesis and characteristic morphologic abnormalities of the erythroblasts. Three major types have been described based on characteristic morphologic abnormalities of the erythroblasts, and the molecular approach for the causative genes. CDA type 1 is inherited as autosomal recessive disorder caused mainly by mutation in CDAN1 gene encoding the codanin-1 protein. More than 100 cases have been described, the severity of anemia varies considerably. Nonhematologic dysmorphologies may be present. Therapy includes redcell transfusion,iron chelation therapy, interferon alpha (INF alpha) and allogenic stem cell transplantation.Congenital dyserythropoietic anemias (CDAs) are a groupof rare hereditary congenital anemias characterized bymarked ineffective erythropoiesis and characteristicmorphologic abnormalities of the erythroblasts. Threemajor types have been described based on characteristicmorphologic abnormalities of the erythroblasts, and themolecular approach for the causative genes. CDA type 1 isinherited as autosomal recessive disorder caused mainlyby mutation in CDAN1 gene encoding the codanin-1protein. More than 100 cases have been described, theseverity of anemia varies considerably. Nonhematologicdysmorphologies may be present. Therapy includes redcelltransfusion, iron chelation therapy, interferon alpha(INF alpha) and allogenic stem cell transplantation. Aims: Methods: We are reporting two transfusion dependent siblings diagnosed with CDA type 1, including their treatment with IFN and outcome. We are reporting two transfusion dependent siblingsdiagnosed with CDA type 1, including their treatment withIFN and outcome. Results: We are reporting 2 boy siblings with CDA type 1 who were referred for bone marrow transplantation at our center at the ages of 11 and 12 years. They have first-degree consanguineous parents and were born with low birth weight (1677 gm and 1500 gram, respectively) and have been transfusion dependent since birth. They were diagnosed using genetic testing and were found to be homozygous at C150RF41, consistent with a diagnosis of CDAN1B. They both had short stature and mild splenomegaly but no dysmorphism. Their ferritin levels at time of referral was 1500 ng/ml and 1220 ng/ml respectively. Bone marrow evaluation showed erythroid precursors are quantitatively increased. The erythroid maturation is megaloblastoid and show binucleation in 10% to 15% of the erythroid cells. They were started on interferon-Alfa-2a as one million unit weekly, with excellent response, no blood transfusion requirement since starting therapy, and iron chelation has been stopped. Due to shortage in the interferon-alpha 2a, a once monthly Pegylated interferon alpha was started for both patients with excellent response without toxicity. Summary/Conclusion: We report 2 Jordanian siblings with transfusion dependent CDA-1 caused a homozygous mutation of C150RF41 gene. They both showed dramatic response to IFN-alpha treatment which was maintained for at more than 2 years with no toxicity.